6i6r - Revision history

OCA at 11:48, 24 January 2024

OCA — Wed, 24 Jan 2024 11:48:03 GMT

←Older revision		Revision as of 11:48, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6i6r' size='340' side='right'caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>		<StructureSection load='6i6r' size='340' side='right'caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6I6R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I6R FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H62:(1~{R},2~{R},3~{R},4~{S},6~{S})-6-azanyl-2,3,4-tris(oxidanyl)cyclohexane-1-carboxylic+acid'>H62</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.02Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-iduronidase L-iduronidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.76 3.2.1.76] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H62:(1~{R},2~{R},3~{R},4~{S},6~{S})-6-azanyl-2,3,4-tris(oxidanyl)cyclohexane-1-carboxylic+acid'>H62</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6i6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6r OCA], [~~http~~://pdbe.org/6i6r PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6i6r RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6i6r PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6r ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6i6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6r OCA], [https://pdbe.org/6i6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i6r RCSB], [https://www.ebi.ac.uk/pdbsum/6i6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6r ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN]] Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:[~~http~~://omim.org/entry/607014 607014]]; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.<ref>PMID:8019563</ref> <ref>PMID:8401515</ref> <ref>PMID:8328452</ref> <ref>PMID:1301941</ref> <ref>PMID:7951228</ref> <ref>PMID:7550232</ref> <ref>PMID:7550242</ref> <ref>PMID:1946389</ref> <ref>PMID:10466419</ref> <ref>PMID:10735634</ref> <ref>PMID:12559846</ref> <ref>PMID:15300847</ref> <ref>PMID:21394825</ref> Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:[~~http~~://omim.org/entry/607015 607015]]; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:[~~http~~://omim.org/entry/607016 607016]]; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.	+	[https://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN] Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:[https://omim.org/entry/607014 607014]; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.<ref>PMID:8019563</ref> <ref>PMID:8401515</ref> <ref>PMID:8328452</ref> <ref>PMID:1301941</ref> <ref>PMID:7951228</ref> <ref>PMID:7550232</ref> <ref>PMID:7550242</ref> <ref>PMID:1946389</ref> <ref>PMID:10466419</ref> <ref>PMID:10735634</ref> <ref>PMID:12559846</ref> <ref>PMID:15300847</ref> <ref>PMID:21394825</ref> Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:[https://omim.org/entry/607015 607015]; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:[https://omim.org/entry/607016 607016]; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: L-iduronidase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gloster~~, T M~~]]	+	[[Category: Gloster TM]]
-	[[Category: McMahon~~, S A~~]]	+	[[Category: McMahon SA]]
-	[[Category: Oehler, V]]	+	[[Category: Oehler V]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Iduronidase inhibitors gh39~~]]	+

OCA at 17:21, 14 August 2019

OCA — Wed, 14 Aug 2019 17:21:25 GMT

←Older revision		Revision as of 17:21, 14 August 2019
Line 1:		Line 1:

	==New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes==		==New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes==
-	<StructureSection load='6i6r' size='340' side='right' caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>	+	<StructureSection load='6i6r' size='340' side='right'caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6R FirstGlance]. <br>		<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6R FirstGlance]. <br>
Line 25:		Line 25:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: L-iduronidase]]		[[Category: L-iduronidase]]
		+	[[Category: Large Structures]]
	[[Category: Gloster, T M]]		[[Category: Gloster, T M]]
	[[Category: McMahon, S A]]		[[Category: McMahon, S A]]

OCA at 08:27, 6 March 2019

OCA — Wed, 06 Mar 2019 08:27:43 GMT

←Older revision		Revision as of 08:27, 6 March 2019
Line 1:		Line 1:

	==New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes==		==New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes==
-	<StructureSection load='6i6r' size='340' side='right' caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>	+	<StructureSection load='6i6r' size='340' side='right' caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6R FirstGlance]. <br>		<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6R FirstGlance]. <br>

OCA at 06:48, 5 December 2018

OCA — Wed, 05 Dec 2018 06:48:05 GMT

←Older revision		Revision as of 06:48, 5 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6i6r is ~~ON HOLD~~	+	==New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes==
		+	<StructureSection load='6i6r' size='340' side='right' caption='[[6i6r]], [[Resolution\|resolution]] 2.02Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6i6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6R FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H62:(1~{R},2~{R},3~{R},4~{S},6~{S})-6-azanyl-2,3,4-tris(oxidanyl)cyclohexane-1-carboxylic+acid'>H62</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-iduronidase L-iduronidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.76 3.2.1.76] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6r OCA], [http://pdbe.org/6i6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i6r RCSB], [http://www.ebi.ac.uk/pdbsum/6i6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6r ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/IDUA_HUMAN IDUA_HUMAN]] Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:[http://omim.org/entry/607014 607014]]; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.<ref>PMID:8019563</ref> <ref>PMID:8401515</ref> <ref>PMID:8328452</ref> <ref>PMID:1301941</ref> <ref>PMID:7951228</ref> <ref>PMID:7550232</ref> <ref>PMID:7550242</ref> <ref>PMID:1946389</ref> <ref>PMID:10466419</ref> <ref>PMID:10735634</ref> <ref>PMID:12559846</ref> <ref>PMID:15300847</ref> <ref>PMID:21394825</ref> Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:[http://omim.org/entry/607015 607015]]; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:[http://omim.org/entry/607016 607016]]; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cyclophellitol aziridines are potent irreversible inhibitors of retaining glycosidases and versatile intermediates in the synthesis of activity-based glycosidase probes (ABPs). Direct 3-amino-2-(trifluoromethyl)quinazolin-4(3H)-one-mediated aziridination of l-ido-configured cyclohexene has enabled the synthesis of new covalent inhibitors and ABPs of alpha-l-iduronidase, deficiency of which underlies the lysosomal storage disorder mucopolysaccharidosis type I (MPS I). The iduronidase ABPs react covalently and irreversibly in an activity-based manner with human recombinant alpha-l-iduronidase (rIDUA, Aldurazyme((R)) ). The structures of IDUA when complexed with the inhibitors in a non-covalent transition state mimicking form and a covalent enzyme-bound form provide insights into its conformational itinerary. Inhibitors 1-3 adopt a half-chair conformation in solution ((4) H3 and (3) H4 ), as predicted by DFT calculations, which is different from the conformation of the Michaelis complex observed by crystallographic studies. Consequently, 1-3 may need to overcome an energy barrier in order to switch from the (4) H3 conformation to the transition state ((2, 5) B) binding conformation before reacting and adopting a covalent (5) S1 conformation. rIDUA can be labeled with fluorescent Cy5 ABP 2, which allows monitoring of the delivery of therapeutic recombinant enzyme to lysosomes, as is intended in enzyme replacement therapy for the treatment of MPS I patients.

-	~~Authors: Gloster, T~~.M., McMahon~~, S.A.~~, Oehler, V.	+	New Irreversible alpha-l-Iduronidase Inhibitors and Activity-Based Probes.,Artola M, Kuo CL, McMahon SA, Oehler V, Hansen T, van der Lienden M, He X, van den Elst H, Florea BI, Kermode AR, van der Marel GA, Gloster TM, Codee JDC, Overkleeft HS, Aerts JMFG Chemistry. 2018 Oct 11. doi: 10.1002/chem.201804662. PMID:30307091<ref>PMID:30307091</ref>

-	~~Description: New Irreversible~~ a-l-~~Iduronidase Inhibitors and Activity-Based Probes~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Gloster, T.M]]	+	<div class="pdbe-citations 6i6r" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: L-iduronidase]]
		+	[[Category: Gloster, T M]]
		+	[[Category: McMahon, S A]]
	[[Category: Oehler, V]]		[[Category: Oehler, V]]
-	[[Category: ~~Mcmahon, S.A~~]]	+	[[Category: Hydrolase]]
		+	[[Category: Iduronidase inhibitors gh39]]

OCA: Protected "6i6r" [edit=sysop:move=sysop]

OCA — Sun, 02 Dec 2018 18:39:40 GMT

Protected "6i6r" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:39, 2 December 2018

OCA: New page: '''Unreleased structure''' The entry 6i6r is ON HOLD Authors: Gloster, T.M., McMahon, S.A., Oehler, V. Description: New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probe...

OCA — Sun, 02 Dec 2018 18:39:39 GMT

New page: '''Unreleased structure''' The entry 6i6r is ON HOLD Authors: Gloster, T.M., McMahon, S.A., Oehler, V. Description: New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probe...

New page

'''Unreleased structure'''

The entry 6i6r is ON HOLD

Authors: Gloster, T.M., McMahon, S.A., Oehler, V.

Description: New Irreversible a-l-Iduronidase Inhibitors and Activity-Based Probes
[[Category: Unreleased Structures]]
[[Category: Gloster, T.M]]
[[Category: Oehler, V]]
[[Category: Mcmahon, S.A]]